In summary, ultrasmall gold nanoparticles are able to cross the blood–brain barrier in these in vitro human brain cell spheroids, consisting of six different cell types. This is of high interest, e.g. for future therapies to deliver functional drugs into the brain. Together with our earlier observation that such nanoparticles can enter cells and also the cell nucleus (in contrast to the dissolved dye)28,30, this opens a potential pathway for targeted therapies inside the brain which are not possible with water-dissolved drugs. However, while the toxicity was very low in this model, a study of cumulative injury in animal models will be required to better predict applications in humans, since the clearance kinetics of the particles are still unknown.